Doxycycline Inhibition of a Pseudotyped Virus Transduction Does Not Translate to Inhibition of SARS-CoV-2 Infectivity

Autor: Luisa Diomede, Sara Baroni, Ada De Luigi, Arianna Piotti, Jacopo Lucchetti, Claudia Fracasso, Luca Russo, Valerio Bonaldo, Nicolò Panini, Federica Filippini, Fabio Fiordaliso, Alessandro Corbelli, Marten Beeg, Massimo Pizzato, Francesca Caccuri, Marco Gobbi, Emiliano Biasini, Arnaldo Caruso, Mario Salmona
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Viruses, Vol 13, Iss 9, p 1745 (2021)
Druh dokumentu: article
ISSN: 1999-4915
DOI: 10.3390/v13091745
Popis: The rapid spread of the pandemic caused by the SARS-CoV-2 virus has created an unusual situation, with rapid searches for compounds to interfere with the biological processes exploited by the virus. Doxycycline, with its pleiotropic effects, including anti-viral activity, has been proposed as a therapeutic candidate for COVID-19 and about twenty clinical trials have started since the beginning of the pandemic. To gain information on the activity of doxycycline against SARS-CoV-2 infection and clarify some of the conflicting clinical data published, we designed in vitro binding tests and infection studies with a pseudotyped virus expressing the spike protein, as well as a clinically isolated SARS-CoV-2 strain. Doxycycline inhibited the transduction of the pseudotyped virus in Vero E6 and HEK-293 T cells stably expressing human receptor angiotensin-converting enzyme 2 but did not affect the entry and replication of SARS-CoV-2. Although this conclusion is apparently disappointing, it is paradigmatic of an experimental approach aimed at developing an integrated multidisciplinary platform which can shed light on the mechanisms of action of potential anti-COVID-19 compounds. To avoid wasting precious time and resources, we believe very stringent experimental criteria are needed in the preclinical phase, including infectivity studies with clinically isolated SARS-CoV-2, before moving on to (futile) clinical trials.
Databáze: Directory of Open Access Journals
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